The serological hallmark of the altered immunological status of patients with systemic lupus erythematosus (SLE) is the presence of antibodies in the sera of these patients to a variety of autoantigens: most notably DNA and DNA histone. Our laboratory has engaged in the study of a class of antigen-antibody systems which occur characteristically in these patients and which involve soluble antigens which do not contain DNA or DNA conjugates. These reactions have been characterized by their precipitin reactions in agar gels between SLE sera and crude tissue extracts. The focal point of this proposal is the purification of these antigens and the detailed assessmnt of immune responses to the nonDNA containing antigens in SLE patients. Some of these antigens are nuclear (nuclear RNP and Sm) and others are cytoplasmic (cytoplasmic RNP and Ro). The availability of purified antigens will permit the measurement of cell mediated immunity to these antigens as well as shed more light on the molecular nature of these antigens. It will also permit the development of more sensitive and quantitative assays for the detection of antibody to these antigens. Assessment of both humoral and cellular immunity to these antigens will lead to a better understanding of the significance of these reactions in the clinical evaluation of SLE patients and may also lead to a better understanding of the abnormal regulation of the immune response characteristic of these patients.